Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXX

DOB: XX Feb 1937

Collection Date: XX Aug 2019

Page 1 of 4Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and confidential

health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.com

HCA Agena Result

RECEIVING HEALTHCARE PROVIDERProvider's Name

SPECIMENSpecimen Type: Buccal Collection Date: XX Aug 2019 Accession Date: XX Aug 2019 Received Date: XX Aug 2019 Report Date: XX Aug 2019

PATIENTName: NameDate of Birth: XX Feb 1937Gender: FAccession #: XXXXXFile: XXXXX

ORDERING PHYSICIAN: Physician's Name

CLINICAL BACKGROUND / INDICATIONS:

RESULT: POSITIVE - CLINICALLY SIGNIFICANT VARIANT IDENTIFIED

Note: "CLINICALLY SIGNIFICANT", as defined in the report, is a genetic change that has been directlyreported to contribute to the development of disease and is associated with the potential to alter medicalintervention.

CLINICALLY SIGNIFICANT VARIANTSNote: "CLINICALLY SIGNIFICANT", as defined in the report, is a genetic change that has been directly reported to contribute to thedevelopment of disease and is associated with the potential to alter medical intervention.

CLASSIFICATION GENE RSID MUTATION INTERPRETATION

Likely Pathogenic MLH3 rs28756990 c.2221G>T (p.Val741Phe)HET

HIGH CANCER RISK

DETAILS ABOUT c.2221G>T (p.Val741Phe): NM_014381.2

ClinVar ID: RCV000005901, RCV000005900

Functional Significance: The heterozygote germline MLH3 variant c.2221G>T is predicted to result in abnormal protein translation of the MLH3 protein at amino acidposition 741 (p.Val741Phe) . Predicted effect(s) on the protein: Missense

Clinical Significance: High Cancer Risk This mutation is associated with increased Cancer risk and should be regarded as clinically significant.

Evidence

Diseases directly associated with MLH3:

Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXX

DOB: XX Feb 1937

Collection Date: XX Aug 2019

Page 2 of 4Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and confidential

health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.com

HCA Agena Result

Endometrial carcinoma (OMIM: 608089) References:Hereditary nonpolyposis colorectal cancer type 7 (OMIM: 614385) References:

No additional pathogenic/likely pathogenic variants found in the panel genes tested (refer to the Test Methodology section of thisreport for a complete list of the genes).

Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXX

DOB: XX Feb 1937

Collection Date: XX Aug 2019

Page 3 of 4Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and confidential

health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.com

HCA Agena Result

SECONDARY FINDINGS: VARIANTS OF UNKNOWN SIGNIFICANCE

GENE MUTATION INTERPRETATION

COLCA1 c.-4506T>G (HET) UNKNOWN

Evidence

Diseases inferred to be associated with COLCA1:

Colorectal Cancer 

RHPN2 c.185+2855A>G (HET) UNKNOWN

Evidence

Function:

colorectal cancer

Note: A Variant of Unknown Significance (VUS) is a change seen in the gene and there is not enough information at this time to support amore definitive classification of this sequence change. These VUS are mainly based on the Trusight Cancer Panel from Illumina. "TruSightCancer includes genes associated with both common (e.g., breast, colorectal) and rare cancers. In addition, the set includes 284 SNPs found tocorrelate with cancer through genome-wide association studies (GWAS). Content selection was based on expert curation of the scientificliterature and other high-quality resources"1.

Risk Estimate should be based on clinical and family history, as the clinical significance of this result is unknown.Genetic testing for variants of unknown significance (VUSs) in family members may be pursued to help clarify VUS significance, butcannot be used to identify at-risk individuals at this time.These results should be interpreted within the context of additional laboratory results, family history, and clinical findings. Geneticcounseling is recommended to discuss the implications of this result. For access to a network of genetic providers, please visitwww.nsgc.org or tagc.med.sc.edu/professional.organizations.asp.

References:

1. https://www.illumina.com/products/by-type/clinical-research-products/trusight-cancer.html

Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXX

DOB: XX Feb 1937

Collection Date: XX Aug 2019

Page 4 of 4Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and confidential

health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.com HCA Agena Result

ADDITIONAL INFORMATIONAssay was performed in a CLIA certified laboratory (CLIA#45D2034851).

METHODOLOGY AND LIMITATIONSThis test is a comprehensive screen of selected variants in 108 genes associated with hereditary cancer predisposition. This array-based assay detects listed alleles, including targeted variants with known clinical significance at analytical sensitivity and specificity >99%. Variants were classified following recent guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

The genes in this panel are: ABCB1 ACTRT3 AIMP2 AKT1 ALK FLACC1 APC AR ARHGAP44 ATF1 ATM AXIN2 BAG6 BMPR1A BRAF BRCA1 BRCA2 BRIP1 BUB1B CASC17 CASC8 CCHCR1 CDH1 CDK10 CDKN1A CDKN2A CHEK2 CHRNA3 CLPTM1L COLCA1 CTD-2194D22.4 DBNDD1 DICER1 EGFR EHBP1 ELAC2 EPCAM ETS2 FGF10 FGFR4 FH FLCN HNF1B HPDL HYKK IRF1 ITGA6 KLK3 KRAS LAMA5 LMTK2 MAP2K7 MAP4K2 MAX MEN1 MIR5580 MITF MLH1 MLH3 MLPH MSH2 MSH6 MSMB MSR1 MTAP MUTYH MXI1 NF1 NUDT11 PADI6 PALB2 PCAT2 PDLIM5 PIGU PMS2 POU5F1B PTEN RAD51 RAD54B RAD54L RB1 RET RFX6 RHPN2 RNA5SP299 RNASEL RNU1-19P RRAS2 RUNX1 SDHB SDHC SDHD SLC22A3 SMAD4 SMAD7 STK11 TERT THADA TMEM127 TP53 TP63 TSC1 TUBB3 VHL WEE1 XRCC1 XXYLT1 MT-ND3

Details About Non-Clinically Significant Variants: All individuals carry DNA changes (i.e., variants) and most variants do not increase an individual's risk of Cancer or other diseases. When identified, variants of uncertain significance (VUS) are reported. Likely benign variants (Favor Polymorphisms) and benign variants (Polymorphisms) are not reported and available data indicate that these variants most likely do not cause increased Cancer risk. Present evidence does not suggest that non-clinically significant variant findings be used to modify patient medical management beyond what is indicated by the personal and family history and any other significant clinical findings.

Limitations: This test will not detect all the known alleles that result in altered or inactive tested genes. This test does not account for all individual variations in the individual tested. Absence of a detectable gene mutation does not rule out the possibility that a patient has different phenotypes due to the presence of an undetected polymorphism or due to other factors such as drug-gene interactions, comorbidities and lifestyle habits.

Disclaimer: The information presented on this report is provided as general educational health information. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Ayass Lung Clinic, PLLC developed this test and its performance characteristics. This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Ayass Lung Clinic, PLLC is accredited by CLIA for performance of high complexity testing. The HCA report is one of multiple pieces of information that clinicians should consider in providing medical advice for each patient. This test should be interpreted in context with other clinical findings. It remains the responsibility of the health-care provider to interpret the results of the test.

These assays do not detect polymorphisms other than those outside of the panel. Rare false positive or false negative results may occur. These assays have been developed and performance characteristics determined by Ayass Lung Clinic, PLLC; and therefore, are classified as Laboratory Developed Tests. These assays have not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance is not necessary. Ayass Lung Clinic, PLLC is accredited by CLIA for performance of high complexity testing. These tests are used for clinical purposes and should not be considered as investigational. Results of genotyping should be interpreted in the full context of the patient's clinical history, including hepatic and renal function, life style, co-administration of other drugs, and other pre-existing conditions.

The source of the variants selected include ClinVar, dbSNP, CIVIC, and Illumina Trusight cancer panel. The report has two sections: ClinVar pathogenic SNPs and non ClinVar (Trusight panel GWAS snps). Trusight SNPs are mostly intronic SNPs which could play a role inpromoter/enhancer activity. They are based on Genome Wide Association Studies and caution must be taken to understand the relevance of these SNPs. This report was produced using TGex, software licensed by LifeMap Sciences.

Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXXX

DOB: XX Jul 1936 Collection

Date: XX Jun 2019

Page 1 of 2Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and confidential

health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.comHCA Agena Result

RECEIVING HEALTHCARE PROVIDERProvider's Name

SPECIMENSpecimen Type: Buccal Collection Date: XX Jun 2019 Accession Date: XX Jun 2019 Received Date: XX Jun 2019 Report Date: XX Jun 2019

PATIENTName: NameDate of Birth: XX Jul 1936Gender: FAccession #: XXXXXXFile: XXXXXX

ORDERING PHYSICIAN: Physician's Name

CLINICAL BACKGROUND / INDICATIONS:

RESULT: NEGATIVE---NO CLINICALLY SIGNIFICANT MUTATION IDENTIFIED

Note: "CLINICALLY SIGNIFICANT", as defined in the report, as a genetic change that is associated with thepotential to alter medical intervention.

All 103 genes listed in the Test Methodology section of this report have been evaluated for the presence of selected genetic variants that may predispose to cancer. No pathogenic (disease causing) or likely pathogenic genetic changes (mutations) have been identified. No further medical action is necessary. However, behavioral counseling on lifestyle changes to mitigate environmental risks is encouraged. Cancer development is multifactorial, often involving an interplay of genetic and environmental risk factors. Relevant lifestyle changes (where applicable) are recommended, for instance:

Cessation of smokingLimited alcohol consumptionRegular exerciseHealthy diet and weight managementLimited exposure to UV rays

Hereditary Cancer Screening Result

Patient Name: Name

Accession #: XXXXXX

DOB: XX Jul 1936 Collection

Date: XX Jun 2019

Page 2 of 2Test Performed at Ayass Bioscience, LLC, doing business as Ayass Lung Clinic PLLC. This laboratory is certified under the CLIA-88 as qualified to perform high complexity clinical testing. This document contains private and

confidential health information protected by state and federal law.

Lab Director: Dr. Ihsan Housini, MD | CLIA: 45D2034851 | 8501 Wade Blvd, Bldg 9, Frisco TX 75034 | 972-668-6005 | www.AyassBioscience.com HCA Agena Result

ADDITIONAL INFORMATIONAssay was performed in a CLIA certified laboratory (CLIA#45D2034851).

METHODOLOGY AND LIMITATIONSThis test is a comprehensive screen of selected variants in 108 genes associated with hereditary cancer predisposition. This array-based assay detects listed alleles, including targeted variants with known clinical significance at analytical sensitivity and specificity >99%. Variants were classified following recent guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

The genes in this panel are: ABCB1 ACTRT3 AIMP2 AKT1 ALK FLACC1 APC AR ARHGAP44 ATF1 ATM AXIN2 BAG6 BMPR1A BRAF BRCA1 BRCA2 BRIP1 BUB1B CASC17 CASC8 CCHCR1 CDH1 CDK10 CDKN1A CDKN2A CHEK2 CHRNA3 CLPTM1L COLCA1 CTD-2194D22.4 DBNDD1 DICER1 EGFR EHBP1 ELAC2 EPCAM ETS2 FGF10 FGFR4 FH FLCN HNF1B HPDL HYKK IRF1 ITGA6 KLK3 KRAS LAMA5 LMTK2 MAP2K7 MAP4K2 MAX MEN1 MIR5580 MITF MLH1 MLH3 MLPH MSH2 MSH6 MSMB MSR1 MTAP MUTYH MXI1 NF1 NUDT11 PADI6 PALB2 PCAT2 PDLIM5 PIGU PMS2 POU5F1B PTEN RAD51 RAD54B RAD54L RB1 RET RFX6 RHPN2 RNA5SP299 RNASEL RNU1-19P RRAS2 RUNX1 SDHB SDHC SDHD SLC22A3 SMAD4 SMAD7 STK11 TERT THADA TMEM127 TP53 TP63 TSC1 TUBB3 VHL WEE1 XRCC1 XXYLT1 MT-ND3

Details About Non-Clinically Significant Variants: All individuals carry DNA changes (i.e., variants) and most variants do not increase an individual's risk of Cancer or other diseases. When identified, variants of uncertain significance (VUS) are reported. Likely benign variants (Favor Polymorphisms) and benign variants (Polymorphisms) are not reported and available data indicate that these variants most likely do not cause increased Cancer risk. Present evidence does not suggest that non-clinically significant variant findings be used to modify patient medical management beyond what is indicated by the personal and family history and any other significant clinical findings.

Limitations: This test will not detect all the known alleles that result in altered or inactive tested genes. This test does not account for all individual variations in the individual tested. Absence of a detectable gene mutation does not rule out the possibility that a patient has different phenotypes due to the presence of an undetected polymorphism or due to other factors such as drug-gene interactions, comorbidities and lifestyle habits.

Disclaimer: The information presented on this report is provided as general educational health information. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Ayass Lung Clinic, PLLC developed this test and its performance characteristics. This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Ayass Lung Clinic, PLLC is accredited by CLIA for performance of high complexity testing. The HCA report is one of multiple pieces of information that clinicians should consider in providing medical advice for each patient. This test should be interpreted in context with other clinical findings. It remains the responsibility of the health-care provider to interpret the results of the test.

These assays do not detect polymorphisms other than those outside of the panel. Rare false positive or false negative results may occur. These assays have been developed and performance characteristics determined by Ayass Lung Clinic, PLLC; and therefore, are classified as Laboratory Developed Tests. These assays have not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance is not necessary. Ayass Lung Clinic, PLLC is accredited by CLIA for performance of high complexity testing. These tests are used for clinical purposes and should not be considered as investigational. Results of genotyping should be interpreted in the full context of the patient's clinical history, including hepatic and renal function, life style, co-administration of other drugs, and other pre-existing conditions.

The source of the variants selected include ClinVar, dbSNP, CIVIC, and Illumina Trusight cancer panel. The report has two sections: ClinVar pathogenic SNPs and non ClinVar (Trusight panel GWAS snps). Trusight SNPs are mostly intronic SNPs which could play a role inpromoter/enhancer activity. They are based on Genome Wide Association Studies and caution must be taken to understand the relevance of these SNPs. This report was produced using TGex, software licensed by LifeMap Sciences.